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ASSESSMENT OF THE LEVEL OF ORGANOTROPIC AUTOANTIBODIES
IN NEWBORNS WITH LOW BODY WEIGHT
Khursanoy Аkramova
1
, Diloram Akhmedova
2
, Zarina Khaybullina
Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
1
Republican Specialized Scientific and Practical Medical Center of
Pediatrics,Tashkent, Uzbekistan
2
The urgency of the problem
.
The frequency of preterm birth is variable, but in most
developed countries in recent decades it has been quite stable and amounts to 5-10%
of the number of children born[18,29,35].
The frequency of adverse outcomes among
surviving children born before 28 weeks of gestation reaches 40–50%, rising to 70–
90% for children weighing 500.0–750.0 g[30,32,34,36].
In children born with low
div weight, mortality reaches 30% [8,30]. The current level of development of
perinatology makes it possible to increase the survival of these children, but the
peculiarities of their subsequent growth and development require no less attention.
[8].
The fact of premature birth of children in women with a burdened obstetric-
gynecological and somatic history is associated with perinatal CNS damage and often
with a change in the vegetative status of a child in the first years of life. [9,37,41].
In
early childhood and in subsequent periods of development, these children show
psychosomatic abnormalities, in particular nocturnal enuresis, prolonged low-grade
fever, tics and obsessive movements, attention deficit hyperactivity disorder, tension
cephalalgia, arterial hypertension, arterial hypotension, biliary dyskinesia, bronchial
asthma, atopic dermatitis[27,39].
An inverse relationship has been shown between
low birth weight and adult blood pressure levels, the likelihood of developing type 2
diabetes, cardiovascular disease, and an excessive response to stress [26,38]. Lack of
motor development in children at 16 years of age is associated with div weight less
than 2 kg at birth. [31].
IQ tests showed that 41% of children born at the 7th month of
pregnancy had worse performance compared to their healthy peers and had learning
problems [41]. Early preterm birth can negatively affect puberty and increase the
chance of adolescent depression [16], as these children may slow down the process of
myelination of the frontal lobe of the brain, which is responsible for motivation,
satisfaction, short-term memory and vision. [35].
Studies conducted among
adolescents born prematurely revealed anomalies in their brain development, namely,
a lack of gray matter in the temporal brain and cerebellum [37].
The birth of children with low div weight is not only a problem of
perinatology, since the prerequisites for many diseases in adults begin in childhood.
Discharged home from the second stage of nursing, a premature and underweight
child has, according to various sources, an average of 4.1 to 5.5 diseases and belongs
to the second - fifth health groups [3].
Most of these children (up to 68%) form the
third health group, characterized by the presence of chronic compensated pathology
[4]. A number of studies have shown that low weight is fixed at the epigenetic level,
that is, not at the DNA level, but at the level of control of genes responsible for
metabolism [6]. The fact is that a person inherits not a trait, but the norm of a trait’s
reaction: how a specific gene can manifest itself under specific conditions[15,21].
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The maturation of the fetus is a consistent implementation of genetic
capabilities in the specific conditions of the existence of the organism, and the
physiological, psychological and social characteristics of a person depend on a
combination of influencing factors, including neuroimmune ones [14]. The
development of the fetus is largely dependent on the state of the mother's immune
system and is regulated by many interleukins, interferons and embryotropic
antibodies of the IgG class. [20].
If pregnancy occurs against the background of
altered immunoreactivity, this may be the reason for stopping the development of
pregnancy, or a trigger for neurological, somatic or endocrine disorders in the
child[15,20,40].
Identification of predisposition to somatic pathology in low birth weight
newborns is relevant in terms of prognosis and targeted prevention of these
conditions. At the same time, a promising direction in preclinical diagnostics is the
determination of organ-specific antibodies.
Considering that somatic pathology of
mothers is of great importance among the causes of preterm pregnancy, it seems
appropriate to screen newborns for the level of organotropic autoantibodies.
The aim of the study was to assess the level of 24 types of organotropic
autoantibodies in newborns with low div weight.
Material and research methods
.
From 2019 to 2020, we examined 64
newborns who were born at a gestational age of 32-37 weeks with low div weight -
1500.0-2499.0 g.
All newborns were divided into 2 groups: those born with a div
weight of 1500.0-1999.0 g at a gestational age of 32-34 weeks (n=26) and those born
at a gestational age of 35-37 weeks with a div weight of 2000.0-2499.0 g (n=38).
The comparison group consisted of healthy full-term newborns weighing more than
2500.0 g, born at 38-40 weeks of gestation (n=12).
All children underwent a standard
clinical examination, as well as a study of the level of autoantibodies to 24
autoantigens - components of the tissues of the brain, heart, liver, intestines, lungs,
kidneys, endothelium, thyroid gland, pancreas, adrenal glands, as well as an
immunoreactivity index. Autoantibodies were determined by solid-phase ELISA on a
Rayto analyzer (China), with ELI-Viscero-24-Test test systems (Immunculus,
Russia). To conduct the entire panel of tests, 0.5 ml of the child's blood serum was
required, blood sampling was performed on the 5th-7th day of life.
Note that the
deviation of the level of autoantibodies from the average level in the standard serum,
expressed in%, is taken as a conditional norm; the conditional norm lies in the range
from (- 20%) to + 10% (green zone).
If the level of autoantibodies in the subject
exceeds that in the standard by 10-20% ((+11) - (+15%) / (-21%) - (-35%)), then this
is interpreted as a relative deviation (yellow zone), if the level of autoantibodies
exceeds the standard by 20% or more (+15% or more; (-35) or more), then this is a
significant deviation (red zone) [9].
Results.
The average age of mothers of low birth weight newborns did not
differ significantly in both groups and amounted to 23.4±1.2 and 25.8±0.9 years,
respectively.
The study of the anamnesis and the presence of somatic diseases in
mothers showed that IDA was observed in 8 (30.8%) and 12 (31.6%) women -
respectively in the 1st and 2nd groups (p>0.05); preeclampsia was significantly more
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common in mothers of the second group: 24 (63.1%) versus 10 (38.5%) (p<0.05);
somatic diseases during pregnancy were detected in 8 (30.8%) and 14 (36.8%)
women of the first and second groups, which was not statistically significant
(p>0.05).
Of the transferred somatic diseases, diseases of the thyroid gland and upper
respiratory tract were most common, while diseases of the cardiovascular system
(arterial hypertension, arrhythmias) were detected in 7.6% and 10.5% and mothers of
groups 1 and 2, respectively, in In general, somatic diseases were in history in 10-
12% of the examined mothers of underweight children, in the control group this
figure was 8.3% (table 1).
Table 1.
Postponed somatic diseases of mothers of low birth weight newborns
Control
group
general
group,
n=64
Mothers
of
newborns of
the 1st group
(n=26)
Mothers
of
newborns
2
groups
(n=38),
Diseases
of
the
cardiovascular
system
1 (8,3%)
6 (9,3%)
2 (7,6%)
4 (10,5%)
Respiratory diseases 1 (8,3%)
8 (12,5%)
3 (11,5%)
5 (13,1%)
Diseases
of
the
stomach
and
intestines
1 (8,3%)
7 (10,9%)
3 (11,5%)
4 (10,5%)
Diseases of the liver
and gallbladder
0
6 (9,3%)*
2 (7,6%)*
4 (10,5%)*
Diseases
of
the
kidneys and urinary
tract
0
7 (10,9%)* 3 (11,5%)*
4 (10,5%)*
Diabetes
2 types
0
1 (1,5%)
0 (%)
1 (2,6%)
Thyroid diseases
0
8 (12,5%)* 4 (15,3%)*
4 (10,5%)*
CNS diseases
0
0
0
0
Diseases
of
the
reproductive system
1 (8,3%)
7 (10,9%)
3 (11,5%)
4 (10,5%)
Note: *-differences are statistically significant relative to the control group
Diseases of the kidneys and urinary tract, liver, thyroid gland were significantly more
common among mothers of low birth weight newborns. There were no organic
diseases of the nervous system in the anamnesis of mothers of underweight children,
however, 6 (23.1%) and 8 (21.1%) women complained of frequent mood swings,
nervousness - respectively in the 1st and 2nd groups ( p>0.05).
The study of general immunoreactivity in terms of the level of total autoantibodies
revealed that in low birth weight newborns there is a significant decrease in this
indicator below the threshold of -35% relative to standard serum. Based on this, we
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can conclude that the immaturity of the immune system and hyporeactivity,
polyclonal immunosuppression, which is typical for chronic intoxication, latent
intracellular
infections,
immunodeficiency.
The
value
of
the
average
immunoreactivity in low birth weight newborns not only went beyond the reference
interval, but was also significantly lower than in the control group, although there
was no difference between groups 1 and 2 (p>0.05), which indicates that the overall
Immunoreactivity in newborns after 32 weeks is reduced regardless of gestational age
and birth weight.
Of all the 24 parameters studied, the average values of autoantibodies of 7 types out
of 24 were at a level exceeding the limits of the "red zone", i.e. a decrease of more
than 35% and an increase of more than 15% relative to standard serum: these are
autoantibodies to components of the nervous tissue - protein S-100, GFAP, myelin
basic protein, native DNA, platelet membrane antigens, antigens to colon cell
membranes , mitochondrial antigens of liver cells (Table 2).
Table 2.
The content of organotropic autoantibodies in low birth weight newborns
Type
of
autoantibodies
Marker function of
autoantibodies
Control
group
group
1
(n=26), p1
group
2
(n=38), p2
Index
of
immunoreactivity
-
12,2±1,1
-35,3
2,7**
-38,3 2,7**
A / t to S100 - a
protein - apoptosis
regulator,
trophic
factor
of
serotonergic neurons
Marker of changes
in the central and
peripheral nervous
system. An increase
in autoantibodies is
accompanied
by
disturbances in the
emotional
and
volitional sphere, in
some
cases
this
increase initiates the
human
papillomavirus
7,4±1,0 54,7±
2,6**
48,6±1,8**,*
A / t to GFAP -
Brain-specific glial
fibrillar
acidic
protein
of
the
intermediate
filaments
of
the
astrocyte
cytoskeleton system
Marker of astroglial
proliferation,
including
reactive
astrogliosis.
5,7±0,3 45,9±
9,4**
62,8±8,8*,**
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A / t to MBP -
myelin basic protein
Marker
of
demyelinating
processes
5,2±0,6 50,3±5,4** 39,7±2,3*,**
A/t
to
double-
stranded DNA
It characterizes the
state of the immune
system, a marker of
infectious-
inflammatory and
autoimmune
processes,
general
immunoreactivity
8,0±2,1 17,1±
2,9**
16,4 ±1,54**
A / t to TrM-03 -
antigens of platelet
membranes
Autoantibodies to
platelets, markers of
changes
in
the
hemostasis system
13,0±3,0 29,4
±1,9**
30,3 ±3,2**
A/t to ScM
Marker of changes
in the walls of the
thick
intestines
9,4±0,6 15,7
±1,3**
16,8 ±1,6**
A / t to HMMP -
antigens
of
liver
mitochondria
Marker of changes
in liver tissue
5,6±0,4 18,7
±2,4**
20,6 ±2,7**
A/t to LuM-02+LuS-
06 – membrane and
cytoplasmic
components of lung
tissue
Markers of changes
in lung tissue
-15,0±
4,1
-21,4± 3,9
-19,7 ±2,5
A/t
to
b2-
glycoprotein I
Characterizes
the
state of the immune
system, a marker
infectious-
inflammatory
and
autoimmune
processes,
cicatricial adhesive
processes
5,1±1,2 8,1± 1,2** 9,05± 1,42**
A/t
to
the
Fc-
fragment of IgG
It characterizes the
state of the immune
system, the intensity
of the production of
immunoglobulins, a
marker
of
infectious-
inflammatory and
-2,8±1,5 -3,1± 1,03
-2,17± 0,61
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autoimmune
processes
A/t to collagen
Characterizes
the
state of the immune
system, a marker of
connective
tissue
destruction,
cicatricial adhesive
changes
-7,2±2,7 -6,7± 1,3
-7,2± 1,2
A / t to CoM-02 -
membrane antigens
of myocardial cells
Marker of changes
in the heart muscle
-9,0±1,0 -14,5± 2,1
-15,8± 1,6
A
/
t
to
b1-
adrenergic receptors
Marker of changes
in the heart muscle
-
12,1±2,4
-18,1
±2,0**
-15,5 ±2,8
A / t to ANCA -
anionic proteins of
vascular
endothelium
Autoantibodies
to
the endothelium, a
marker of vascular
changes similar to
vasculitis
-9,0±1,3 -8,4± 1,5
-10,0 ±1,1
A/t to KiM-05+KiS-
07 – membrane and
cytoplasmic
components
of
kidney tissue
Markers of changes
in kidney tissue
-2,0±0,4 -6,6± 2,3
-6,2± 1,3
A / t to GaM-02 -
membrane antigens
of
the
gastric
mucosa
Marker of changes
in the walls of the
stomach and
small intestine
7,4±1,8 8,3 ±2,4
12,4 ±2,1
A / t to ItM-07 -
membrane antigens
of cells of the small
intestine mucosa
Marker of changes
in the walls of the
stomach and
small intestine
-5,8±1,1 -8,7 ±2,7
-8,5 ±1,6
A / t to HeS-08 -
cytoplasmic antigens
of hepatocytes
markers of changes
in liver tissue
-2,5±1,1 -6,4
±1,2**
-5,6 ±0,5**
A / t to Ins - insulin
Islet Change Marker
Langengars
and
peripheral
insulin
receptors
-9,0±1,0 -9,7 ±2,0
-9,9 ±1,7
A / t to Ins-R -
insulin receptors
Change marker in
islets of Langengars
and
peripheral
insulin
receptors)
-9,5±3,0 -6,8± 1,6
-7,53± 1,4
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A/t to thyroglobulin
Marker
of
thyroiditis
and
changes in
thyroid gland)
-9,0±0,5 -8,7 ±2,2
-7,7 ±1,1
A / t to TSH-R -
TSH receptors
Marker
of
thyroiditis
and
changes in
thyroid gland
7,0±0,4 5,8± 1,9
6,0± 1,5
A / t to AdrM-D / C-
0
-
membrane
antigens of the cells
of the cortical layer
of the adrenal glands
Marker of changes
in
the
adrenal
glands
8,6±3,3 8,9 ±1,85
7,5± 1,8
A / t to Spr-06 -
membrane antigens
of spermatozoa
Marker of changes
in the prostate gland
in
men
and
endometrium
in
women
-
17,0±5,6
-18,8 ±2,5
-18,2 ±2,3
Note: *- differences are statistically significant between groups 1 and 2 at p<0.05.
**-differences are statistically significant from the control group at p<0.05
The level of autoantibodies to the S100 protein exceeded the values in the
control group by 7.3 times and 6.6 times in newborns of groups 1 and 2, respectively,
and in children weighing 1500.0-1999.9 g, this indicator was significantly higher than
in newborns with weighing 2000.0-2500.0g. A similar trend was noted for the MBM,
GFAP.
These results show a fairly high degree of damage to the nervous tissue in low
birth weight newborns against the background of a decrease in the elimination of
products of incomplete catabolism and apoptosis of brain cells. This is also confirmed
by the high level of autoantibodies to double-stranded DNA in low birth weight
newborns, the content of which was increased by 2.1 times relative to the control
group in children of groups 1 and 2.
An increase in autoantibodies to double-stranded
DNA indicates the activation of apoptotic processes in low-weight newborns in all
tissues, when there is a powerful release of excess phospholipid components of the
membranes of destroyed cells and fragments of nuclear DNA, which is the source of
autoantibodies[22].
The increase in these autoantibodies is the result of catabolism,
apoptosis, and reduced elimination of biodegradation products of various molecules
in low birth weight infants. In addition to impaired clearance from intermediate and
end products of catabolic processes against the background of an increase in their
intensity, the accumulation of autoantibodies can have a cytopathic effect.
It is known
that antinuclear antibodies against the nuclear structures of cells have a pronounced
pathogenic potential, disrupting gene transcription [24], which can contribute during
the perinatal period in small children, reducing the adaptive capacity of their div.
An analysis of the spectrum of elevated autoantibodies shows that the most
vulnerable organs in low birth weight newborns are the central nervous system, the
large intestine (increased autoantibodies to ScM), and the liver (increased
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autoantibodies to HMMP). This predisposition to autoaggression to these tissues in
newborns may explain the high incidence of perinatal CNS damage, necrotizing
enterocolitis in these children [8,25], as well as a high tendency to disturbances in the
hemostasis system and a prolonged course of transient conditions - neonatal jaundice.
It is known that the S100 protein is involved in the development of the nervous
system, regulates the migration of neuroblasts in the brain and spinal cord and their
functional differentiation, regulates the processes of intracellular calcium metabolism
and protein phosphorylation, organization of the cytoskeleton, gene transcription,
growth and differentiation of glial cells and neuronsю Its high level in the first 72
hours of life is a marker of a poor prognosis in children with asphyxia of the severity
of cerebral disorders. The growth of antibodies to GFAP-specific protein of astrocyte
filaments - accompanies the proliferation of astroglia in response to inflammation,
damage and oxidative stress
The involvement of the CNS and intestines in damage in preterm infants is also
associated with the presence of a hypoxic component, to which these tissues are
particularly sensitive. [28]. The involvement of liver mitochondria with the
development of oxidative stress and endogenous intoxication during fetal hypoxia
was confirmed by us earlier in the experiment, and disturbances in the phospholipid
spectrum of membranes of microsomal and mitochondrial liver fractions were
detected, which were observed both at birth and up to 21 days of observation of rat
pups that underwent intrauterine hypoxia and premature births with low birth
weight[2, 28].
This once again proves that protein-energy deficiency, along with
hypoxia, is a trigger for an increase in ROS production in the liver, when
mitochondria are the most vulnerable and are the first to turn on, which can provoke
an increase in the production of autoantibodies to them. The presence of
autoantibodies to the components of liver mitochondria (cardiolipin), as well as to the
nervous tissue and intestines, is perhaps another of the mechanisms that contribute to
the damage to organs and tissues in low birth weight newborns long before the
clinical manifestation
We also found an increase in autoantibodies to platelets, the level of which
exceeded the control level by 2.2 times, and, regardless of the gestational age after 32
weeks. The presence of antiplatelet antibodies indicates a predisposition to increased
adhesion and aggregation of platelets and potential microcirculatory disorders, which
play a key role in hypoxic-ischemic lesions of the brain and intestines in preterm
infants both in the early neonatal period and later.
As our results showed, the average values of autoantibodies to 3 tissues: lung,
heart and reproductive system were slightly reduced, in some cases to the threshold
of the "yellow zone", while there were no significant differences between the control
and experimental groups, and the incidence of mothers with diseases of these systems
was also identical in both control and experimental groups. It is possible that the
presence of somatic pathology of the mother leads to insufficient synthesis of
autoantibodies to the affected organs, which may reflect both the insufficient
development of these organs and increased vulnerability to damage.
[1,13].
Autoantibodies have a protective property, tk. bind the degradation products of
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biomolecules, so their decrease is undesirable, it, along with an increase in
autoantibodies, can cause the onset of pathological changes in tissues.
Thus, autoantibodies to the membrane and cytoplasmic components of the lung
tissue in low birth weight newborns were in the "yellow zone", indicating
subthreshold changes that can be realized in bronchopulmonary dysplasia in
newborns, or frequent colds of the upper respiratory tract in children of the first years
of life. Subthreshold changes in these autoantibodies in newborns were combined
with the incidence of bronchopulmonary pathology in mothers of underweight
children.
At the same time, as our observations showed, the frequency of diseases of
the upper and lower respiratory tract was the same in mothers of the control group
and groups 1 and 2, and the level of autoantibodies in their newborns also did not
differ significantly between the control and two observation groups. This suggests a
maternal origin of autoantibodies to lung tissue in newborns.
Also, the maternal origin of autoantibodies is indicated by the fact that
newborns have a subthreshold level of a decrease in autoantibodies to the Spr-06
antigen. This is a common antigen of the membranes of spermatozoa and human
prostate cells, which is not expressed by the cells of the woman's div (gender-
specific antigen). The production of autoantibodies to it occurs in women with
inflammatory diseases of the endometrium and genital tract, a pathological change in
the level of autoantibodies is an indicator of inflammatory diseases in the pelvic
organs in women [22].
It should be noted that the level of autoantibodies to Spr-06 in
newborns did not differ significantly between the control group, groups 1 and 2, and
the frequency of diseases of the reproductive system was also identical in the
experimental and control groups.
The level of cardiospecific autoantibodies to membrane antigens of myocardial
cells and to b1-adrenergic receptors in low birth weight newborns was characterized
by their moderate deficiency in the range of -15% - -18%. Pathological changes in the
level of antibodies to the membrane antigen of cardiomyocytes CoM-015-15 and b1-
adrenergic receptors are markers of the onset of destructive changes in the
myocardium and the conduction system of the heart. It is known from the literature
that a significant deviation of the level of autoantibodies from the reference values
may be associated with metabolic disorders, causing myocardial dysfunction; and
inhibition of the production of cardiospecific autoantibodies was associated with
arrhythmias in children[10,11].
The average level of autoantibodies to the IgG fragment, collagen, anionic
proteins of the vascular endothelium, kidney tissue, stomach, hepatocytes, islets of
Langerhans, insulin and insulin receptor, as well as to thyroglobulin and TSH
receptors were within the reference values and data of the control group. At the same
time, a comparative assessment of the number of children with a pathological level of
autoantibodies in the control group and observation groups 1 and 2 showed that the
number of children with a significant deviation of autoantibodies among low-weight
children is statistically significantly higher than among children in the control group
in almost all studied parameters.
(Table 3).
At the same time, the frequency of
significant deviations was higher (p<0.05) in group 1 relative to group 2 for such
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parameters as autoantibodies to ScM, HMMP, beta-adrenergic receptors, ANCA,
KiM-05+KiS-07, TSH-R, to AdrM -D/C-0, Spr-06.
Table 2.
The frequency of occurrence of a significant deviation from the conditional
norm of organotropic autoantibodies in low birth weight newborns
The nature
of
the
deviations
1
group
(1500-
1999г),
n=26, p1
2
group
(2000-2500г),
n=38, p2
Control group
n
%
n
%
n
%
Index
of
immunoreactivity
Conditional
rate (-20 -
+10)
0
0
0
0
10
83,3
Relative
deviation.
0
0
0
0
2
16,7
significant
deviation 35
+15
26
100
38
100
0
0
A / t to S100 - a
protein - apoptosis
regulator,
trophic
factor
of
serotonergic
neurons
Conditional
rate (-20 -
+10)
0
0
0
0
10
83,3
Relative
deviation
0
0
0
0
1
8,4
significant
deviation.
26
100
38
100
1
8,3
A / t to GFAP -
Brain-specific glial
fibrillar
acidic
protein
of
intermediate
filaments
of
the
astrocyte
cytoskeleton system
Conditional
rate (-20 -
+10)
0
0
0
0
12
100
Relative
deviation.
0
0
0
0
0
0
significant
deviation.
26
100
38
100
0
0
A / t to MBP -
myelin basic protein
Conditional
rate (-20 -
+10)
0
0
0
0
12
100
Relative
deviation
0
0
0
0
0
0
significant
deviation..
26
100
38
100
0
0
A/t
to
double-
stranded DNA
Conditional
rate (-20 -
+10)
5
19,2
5
13,2
9
75
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Relative
deviation.
11 42,3 20
52,6
2
16,7
significant
deviation
10
38,5
*
13
34,2*
1
8,3
A / t to TrM-03 -
antigens of platelet
membranes
Conditional
rate (-20 -
+10)
3
11,5 5
13,2
8
66,7
Relative
deviation.
0,0 0,0
9
23,7
1
8,3
significant
deviation.
23
88,5
*
24
63,2*,
**
3
25,0
A/t to ScM
Conditional
rate (-20 -
+10)
3
11,5 4
10,5
11
91,7
Relative
deviation.
10 38,5 27
71,1
0
significant
deviation.
23
88,5
*
7
18,4*,
**
1
8,3
A / t to HMMP -
antigens of liver
mitochondria
Conditional
rate (-20 -
+10)
3
11,5 4
10,5
12
100
Relative
deviation.
3
11,5 13
34,2
0
0
significant
deviation
20
76,9
*
21
55,3*,
**
0
0
A/t
to
LuM-
02+LuS-06
–
membrane
and
cytoplasmic
components of lung
tissue
Conditional
rate (-20 -
+10)
16
61,5
*
20
52,6*
9
75
Relative
deviation.
0,0 0,0
4
10,5
2
16,7
significant
deviation
10
38,5
*
14
36,8*
1
8,3
A/t
to
b2-
glycoprotein I
Conditional
rate (-20 -
+10)
18 69,2 20
52,6
12
100
Relative
deviation.
8
30,8
*
9
23,7*
0
0
significant
deviation
0,0 0,0
9
23,7*,
*
0
0
A/t
to
the
Fc-
fragment of IgG
Conditional
rate (-20 -
+10)
26
100,
0
38
100,0
12
100
Relative
0,0 0,0
0
0,0
0
0
British Medical Journal Volume-2, No 1
10.5281/zenodo.6322641
144
deviation.
significant
deviation
0,0 0,0
0
0,0
0
0
A/t to collagen
Conditional
rate (-20 -
+10)
26,
0
100,
0
38
100,0
11
91,7
Relative
deviation.
0,0 0,0
0
0,0
0
0
significant
deviation
0,0 0,0
0
0,0
1
8,3
A / t to CoM-02 -
membrane antigens
of myocardial cells
Conditional
rate (-20 -
+10)
13 50,0 29
76,3
10
83,3
Relative
deviation.
8
30,8 2
5,3
0
0
significant
deviation
5
19,2 7
18,4
2
16,7
A
/
t
to
b1-
adrenergic receptors
Conditional
rate (-20 -
+10)
16 61,5 27
71,1
8
66,7
Relative
deviation.
2
7,7
2
5,3
4
33,3
significant
deviation
8
30,8
*
7
18,4*,
**
0
0
A / t to ANCA -
anionic proteins of
vascular
endothelium
Conditional
rate (-20 -
+10)
23 88,5 34
89,5
12
100
Relative
deviation.
0
0,0
2
5,3
0
0
significant
deviation
3
11,5
*
2
5,3*,*
*
0
0
A/t
to
KiM-
05+KiS-07
–
membrane
and
cytoplasmic
components
of
kidney tissue
Conditional
rate (-20 -
+10)
23 88,5 34
89,5
12
100
Relative
deviation.
0
0,0
2
5,3
0
0
significant
deviation
3
11,5
*
2
5,3*,*
*
0
0
A / t to GaM-02 -
membrane antigens
of
the
gastric
mucosa
Conditional
rate (-20 -
+10)
21 80,8 26
68,4
11
91,7
Relative
deviation..
0,0 0,0
4
10,5
0
0
British Medical Journal Volume-2, No 1
10.5281/zenodo.6322641
145
significant
deviation. -
35 +15
5
19,2
*
8
21,1*
1
8,3
A / t to ItM-07 -
membrane antigens
of cells of the small
intestine mucosa
Conditional
rate (-20 -
+10)
23 88,5 35
92,1
12
100
Relative
deviation..
0,0 0,0
0
0,0
0
0
significant
deviation. -
35 +15
3
11,5
*
3
7,9*
0
0
A / t to HeS-08 -
cytoplasmic
antigens
of
hepatocytes
Conditional
rate (-20 -
+10)
23 88,5 36
94,7
12
100
Relative
deviation..
3
11,5 0
0,0
0
0
significant
deviation. -
35 +15
0,0 0,0
2
5,3
0
0
А/т к Ins – insulin
Conditional
rate (-20 -
+10)
23 88,5 34
89,5
12
100
Relative
deviation..
0,0 0,0
0,0
0,0
0
0
significant
deviation. -
35 +15
3
11,5
*
4
10,5*
0
0
A / t to Ins-R -
insulin receptors
Conditional
rate (-20 -
+10)
26,
0
100,
0
34
89,5
12
100
Relative
deviation..
0
0,0
0
0,0
0
0
significant
deviation. -
35 +15
0
0,0
4
10,5
0
0
A/t to thyroglobulin Conditional
rate (-20 -
+10)
23 88,5 38
100,0
12
100
Relative
deviation..
3
11,5 0
0,0
0
0
significant
deviation. -
35 +15
0,0 0,0
0
0,0
0
0
A / t to TSH-R - Conditional
23 88,5 36
94,7
12
100
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146
TSH receptors
rate (-20 -
+10)
Relative
deviation..
0
0,0
0
0,0
0
0
significant
deviation. -
35 +15
3
11,5
*
2
5,3*,*
*
0
0
A / t to AdrM-D /
C-0 - membrane
antigens of the cells
of the cortical layer
of
the
adrenal
glands
Conditional
rate (-20 -
+10)
21 80,8 27
71,1
10
83,3
Relative
deviation..
2
7,7
9
23,7
0
0
significant
deviation. -
35 +15
3
11,5
*
2
5,3*,*
*
2
16,7
A / t to Spr-06 -
membrane antigens
of spermatozoa
Conditional
rate (-20 -
+10)
18 69,2 22
57,9
12
100
Relative
deviation..
0
0,0
0
0,0
0
0
significant
deviation. -
35 +15
8
30,8
*
16
42,1*
0
0
Note: *- differences are statistically significant from the control group at p<0.05
**- differences are statistically significant between groups 1 and 2 at p<0.05
The number of children with a significant deviation in the level of autoantibodies to
the membrane components of the cells of the adrenal cortex (AdrM/D/c-0) was
significantly higher in group 1, both relative to group 2 and control; a similar
situation was observed in the number of children with abnormal levels of
autoantibodies to TSH receptors (TSH-R), autoantibodies to membrane and
cytoplasmic components of the kidney tissue (KiM-0.5 + KiS-0.7), autoantibodies to
anionic proteins of vascular endothelium (ANCA), as well as autoantibodies to beta-
adrenergic receptors and tissue of the large intestine.
As we indicated above, the level
of these autoantibodies was significantly higher in low birth weight infants born at
32–34 weeks of gestation relative to children born at term and at 35–37 weeks of
gestation.
These results indicate an increased susceptibility to damage along with the
CNS, intestines and platelets, as well as the vascular endothelium, kidneys, heart,
adrenal glands and thyroid gland in low birth weight newborns weighing 1500.0-
1999.0 g.
Involvement of the adrenal glands and thyroid gland can also lead to a
violation of the adaptation of these newborns, which must be taken into account in
the rehabilitation program.
We have studied the content of hormones TSH, T3 total, cortisol and ACTH to assess
the adaptive reserve in these newborns. It was found that the level of ACTH in low
birth weight newborns exceeded the control values by 3.1 and 2.6 times in children of
British Medical Journal Volume-2, No 1
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groups 1 and 2, respectively, and the differences between groups 1 and 2 were
statistically significant at p<0.05, and the level of cortisol in low birth weight infants
newborns was significantly reduced, which indicates an insufficient overall adaptive
reserve of the div and tension in the hypothalamic-pituitary-adrenal system(Table
4)
Table 4
The content of hormones in the blood of small newborns
Referenc
e interval
Control
group
group 1 (n=26),
p1
group 2 (n=38),
p2
TSH, mIU/l
1-39
1,84±0,58 4,1±0,2*
3,6±0,2*,**
Т3 total, nmol/l
1,5-11,4
1,66±0,06 1,26±0,03*
1,32±0,02*,**
ACTH, pmol/l
2,2-41,0
22,8±2,8
64,0±2,8*
53,0±1,5*,**
Cortisol, nmol/l
55-304
77,8±6,1
46,8±3,0*
52,9±1,5*
Note: *- differences are statistically significant from the control group at p<0.05;
**- differences are statistically significant between groups 1 and 2 at p<0.05
Thyroid axis status: Studies of thyroid hormones have shown some increase in TSH
with a decrease in total T3 in low birth weight infants. The presence of these shifts
against the background of an increase in autoantibodies to TSH receptors (TSH-R)
and autoantibodies to the membrane components of the cells of the adrenal cortex
(AdrM/D/c-0k) proves the contribution of autoimmunization to these tissues in the
implementation of violations of their functions.
From these results, it can be
concluded that low-birth-weight newborns with abnormal levels of autoantibodies to
endocrine tissues need close attention and monitoring, as well as an individual
rehabilitation program.
An analysis of the results showed that mothers of low birth weight newborns
were significantly more likely to have diseases of the thyroid gland, liver, kidneys,
reproductive system, while the number of children with pathological levels of
autoantibodies to TSH receptors (TSH-R), autoantibodies to membrane and
cytoplasmic components of kidney tissue (KiM-0.5+KiS-0.7) was also significantly
higher among low birth weight infants.
This suggests the contribution of maternal
autoantibodies in these children. The level of organotropic autoantibodies in this
situation partly reflects the immunological pattern of the mother, which can
potentially be realized in the child. There are 2 conflicting views on the origin of
autoantibodies in the fetus. The first is that autoantibodies are high-affinity
immunoglobulins of classes M and G, which have clustering and ontogenetic
dynamics, are synthesized by the fetus, and also penetrate transplacentally from the
mother.
[5].
The reason for this was the detection in the cord blood of a different
palette of autoantibodies, different from the maternal one, which is supplemented by
the transplacental transfer of maternal autoantibodies; in ontogenesis, the spectrum of
autoantibodies is supplemented and diversified; at the same time, the production of
autoantibodies in fetuses has an internal cause, and not only external cross-reacting
antigenic stimuli [23].
The second view of autoantibodies is that they are synthesized
by the fetus, are immunoglobulins M of low affinity and broad specificity, which
recognize both their own and microbial epitopes, are produced by B1a and B1b
British Medical Journal Volume-2, No 1
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lymphocytes (1-5% of the total population); it is a self-sustaining population of B
cells (CD20, CD27, CD43, CD5+, CD70), which are produced in the liver and bone
marrow of the fetus in early ontogenesis, primarily dominate in the serous cavities
and are able to disperse, including into the lamina propria of the gastrointestinal
mucosa and inflammation foci , these lymphocytes have suppressor functions [7].
Our data are more consistent with the first hypothesis, according to which the
autoantidiv fraction is mixed - maternal and fetal.
We have identified autoantibodies to the components of the nervous tissue,
platelets, and intestines in all low birth weight newborns, regardless of the pathology
of these systems in mothers, which indicates the synthesis of these autoantibodies in
the fetuses themselves. The fact that disturbances in the production of ACTH, TSH,
T3 and cortisol were associated with abnormal levels of autoantibodies to these
tissues in newborns indicates a direct damaging effect of autoantibodies.
According to the literature, initially, the increase in autoantibodies is aimed at
increasing the efficiency of the clearance of damaged tissue and activation of
regeneration processes. Identification of persistent anomalies in the content of marker
autoATs of certain specificity makes it possible to analyze the nature of the changes
occurring in the patient's div (including at the stages of pre-illness), more
reasonably approach the prescription of therapy and evaluate the effectiveness and
sufficiency of the treatment.
[12,17].
To do this, it is necessary to identify a risk
group from among low birth weight newborns. Taking into account that the
physiological autoimmune reactions observed in most cases are induced in response
to tissue damage and reflect the compensatory activation of the immune system
aimed at restoring disturbed div homeostasis [19], the detection of an increase in
the level of tissue-specific autoantibodies makes it possible to predict somatic
pathology in a low birth weight newborn.
Thus, the detection of a pathological level
of autoantibodies in low birth weight newborns is necessary to predict the reserve of
their adaptive capabilities and the development of somatic pathology both in the early
neonatal period and in childhood. Also, the detection of autoantibodies to tissues will
allow the choice of therapeutic and rehabilitation tactics.
Conclusions.
1. Total immunoreactivity, assessed by the level of autoantibodies, in newborns
after 32 weeks of gestation is reduced, regardless of gestational age and birth weight.
2. A statistically significant increase in autoantibodies to components of the
nervous tissue: MBP, protein S100, GFAP indicates damage to the nervous tissue in
low birth weight newborns against the background of a decrease in the elimination of
products of incomplete catabolism and apoptosis of brain cells, more pronounced in
children born weighing 1500.0-1999 0 g at 32-34 weeks of gestation.
3.The most pronounced pathological changes in the content of autoantibodies
in low birth weight newborns were found for autoantibodies to the brain, liver
mitochondria, platelets, double stranded DNA, which indicates a greater vulnerability
of these tissues to damage in the neonatal period.
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4. Pathological shifts in the level of autoantibodies to the membrane
components of the cells of the adrenal cortex (AdrM/D/c-0), TSH receptors (TSH-R),
to the membrane and cytoplasmic components of the kidney tissue (KiM-0.5+KiS-
0.7) , anionic proteins of the vascular endothelium (ANCA), to beta-adrenergic
receptors, tissue of the large intestine (ScM), liver mitochondria (HMMP) are
significantly more common in low-weight children born at 32-34 weeks of gestation
relative to children born at term and at 35- 37 weeks of gestation, which indicates an
increased risk of damage to these tissues in low birth weight newborns weighing
1500.0-1999.0 g.
5. Pathological changes in the level of autoantibodies to TSH receptors (TSH-
R) and autoantibodies to the membrane components of the cells of the adrenal cortex
(AdrM/D/c-0k) were combined with an increase in ACTH and TSH against the
background of a decrease in cortisol and T3, which proves the contribution of
autoimmunization to these tissues in violation of their functions.
6. The presence of somatic pathology in mothers (pathology of the respiratory,
circulatory, reproductive system) was combined with the presence of pathological
abnormalities in the level of the corresponding organotropic autoantibodies in
newborns, which proves the influence of the mother's health status on the level of
autoantibodies in newborns.
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